Leukemia is a cancer of the bone marrow involving the developing white blood cells. Based on disease phenotype, leukemia is divided into myeloid and lymphoid, while based on clinical progression it is also categorized into acute and chronic. Approximately 12,330 new cases of acute myeloid leukemia (AML) and 5,330 new cases of acute lymphoid leukemia (ALL) will be diagnosed in the U.S. in 2010 (according to the Leukemia and Lymphoma Society). Leukemia is often associated with specific, recurrent chromosome translocations and inversions that generate fusion genes, which play critical roles in leukemogenesis.
The Core Binding Factor (CBF) subgroup of leukemia contains CBF fusion genes which have been shown to play critical roles in leukemia development. The CBF family is composed of four proteins, the three a subunits, RUNX1 (AML1, Cbfa2), RUNX2 (Cbfa1), and RUNX3 (Cbfa3), and the single β subunit, CBFβ. CBF leukemias contain chromosome abnormalities affecting CBFβ and RUNX1, which account for approximately 20-30% of all acute myeloid leukemia (AML). Using current state-of-the-art therapy, the 5-year survival rate for CBF leukemias is only around 50%.